The major purpose of this Assay Development Proposal is to provide a key step in a fully integrated effort towards the goal of finding small molecule pharmacological tools for the Galanin 3 Receptor. The Scripps Research Institute (TSRI) is a center of excellence in chemistry and biology and its investigators have a strong record of success in identifying and characterizing small molecule pharmacological tools. The Scripps Molecular Libraries Screening Center (MLSC) is taking an active role supporting the NIH Roadmap's effort to identify useful molecular tools. To create excellent small molecule discovery opportunities for eventual submission to the MLSC Network through the X01 application mechanism, we would like to enhance critical basic receptor tools for a clinically important neuroscience target, and ready this system for high throughput biology. 1. Develop a GALR3 beta-lactamase reporter assay and counter screens for high throughput screening. 2. Format and validate the GALR3 antagonist assay for HTS 3. Define the pathway for evaluating HTS derived compound leads in vitro and in vivo Galanin is a neuropeptide with three GPCRs (GALR1-3) that mediates its effects in the brain and peripheral nervous system. GALR3 represents a novel target for antidepressant drug action and there is a great medical need for antidepressants with new mechanism of action. Potent, specific and bioavailable GALR3 antagonists are needed to further validate this target for the treatment of anxiety and depression. Compounds with the desired profile of high potency, selectivity and ability to cross the blood-brain barrier (BBB) will be evaluated in animal models of anxiety and depression. Proof of concept (POC) studies with Galanin receptor agonists and antagonists may ultimately lead to improved therapeutic modalities for several neurological diseases.